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Previous Volume 347:1625-1626 November 14, 2002 Number 20 Next

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To the Editor: In his Clinical Practice article (July 4 issue),¹ Antin does not discuss an important cause of late death after hematopoietic stem-cell transplantation: invasive fungal infection. Several centers have reported that such infections (such as invasive aspergillosis) occur in up to 15 percent of recipients of allogeneic hematopoietic stem-cell transplants and are most commonly encountered in the late phase.² Chronic graft-versus-host disease and therapy with corticosteroids are important risk factors for these infections.² With increasing treatment options that include azole antifungal agents, aggressive diagnostic workup and treatment should be pursued; prophylaxis with azoles in patients at highest risk is under investigation.

Although Antin endorsed the use of valganciclovir for the treatment of cytomegalovirus infection, we caution against its use for preemptive therapy or treatment of cytomegalovirus disease in patients with graft-versus-host disease of the gut, since absorption has not been demonstrated in these patients and since the viral-replication time in vivo is likely to be short. Induction treatment with intravenous ganciclovir should be considered for patients with high levels of immunosuppression or gastrointestinal graft-versus-host disease until ongoing pharmacokinetic and phase 3 efficacy studies better define the role of valganciclovir in recipients of stem-cell transplants.

Michael Boeckh, M.D.
W. Garrett Nichols, M.D.
Kieren A. Marr, M.D.
Fred Hutchinson Cancer Research Center
Seattle, WA 98109-1024
mboeckh{at}fhcrc.org

Editor's note: Drs. Boeckh and Nichols have reported that they have received honorariums from Roche for speaking and consulting.

References

1. Antin JH. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 2002;347:36-42. [Free Full Text]
2. Grow WB, Moreb JS, Roque D, et al. Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplant 2002;29:15-19. [CrossRef][ISI][Medline]

To the Editor: I appreciate Boeckh and colleagues' comment that invasive fungal infections may occur after transplantation. Certainly, anyone who is immunocompromised, especially during long-term corticosteroid therapy, is at risk for invasive fungal infections. The risk of invasive fungal infections is highest early after transplantation and declines with time. For instance, in the study by Grow et al. that is cited by Boeckh and colleagues, there were nine documented cases and five suspected cases, and the median time to the development of invasive fungal infection was 92 days (range, 31 to 459). In addition, one must consider nocardia, actinomyces, and a variety of other unusual organisms in these patients. The use of agents such as voriconazole and posaconazole with activity against filamentous fungi is an important subject for study but not a recommendation that can be made on the basis of available data.

I agree with Boeckh and colleagues' comments regarding the treatment of cytomegalovirus infection, but I would also underscore, in this context, my previous recommendation that patients with clinically significant graft-versus-host disease be cared for by physicians experienced in transplantation.

Finally, in Table 2 of my article, an error regarding the timing of immunizations after transplantation should be corrected. Each "or" in the second column of the table should be replaced by "and" (such that the entries read "12, 14, and 24 months" and "12 and 24 months").

Joseph H. Antin, M.D.
Dana–Farber Cancer Institute
Boston, MA 02115
joseph_antin{at}dfci.harvard.edu

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This article has been cited by other articles:

• Einsele, H., Reusser, P., Bornhauser, M., Kalhs, P., Ehninger, G., Hebart, H., Chalandon, Y., Kroger, N., Hertenstein, B., Rohde, F., for the EBMT Working Group on Infectious Disease, (2006). Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 107: 3002-3008 [Abstract] [Full Text]